The SIV/Macaque Research Core will provide the expertise to evaluate novel therapeutics and surrogate markers in the era of highly active antiretroviral therapy (HAART) in a rigorous, validated animal model that recapitulates HIV CMS infection either in the absence or presence of HAART. Priority for testing will be based on how well the drug meets the established criteria. The Clinical Outcomes Core will be essential to translate novel therapeutics from the animal model into human clinical trials through it multiple connections to the Neuro-AIDS trial consortia. The SIV/Macaque Research Core will play a central role in the current JHU NIMH Center, and will interact with many of the other Cores. This Core will serve the following functions: 1) To evaluate candidate therapeutics identified in the Therapeutic Development Sub-Core or by investigators in the NIMH Center or external investigators in cultured primary macaque cells (lymphocytes, monocyte/macrophages, astrocytes and neural progenitor cells or neuroprogenitor-derived neurons) to determine whether it is appropriate to test the drugs in the SIV macaque model. 2) To provide the resources and expertise necessary to evaluate novel antioxidant/neuroprotective therapeutics in vivo in a rapid, validated SIV macaque model to provide "proof of concept" in vivo. The results of such studies will provide the scientific basis for larger studies in macaques (to delineate pathogenesis and mechanism, funded separately) and/or human clinical trials. 3) To collaborate with the Clinical Outcomes Core on novel therapeutics that show efficacy in the SIV/macaque model to initiate human clinical trials. 4) To collaborate with the Surrogate Marker Core on newly identified surrogate markers for HIV CNS disease, characterizing the pathological basis for the marker in the SIV/macaque model.